title: The healing of alkali-injured cornea is stimulated by a novel matrix regenerating agent (RGTA, CACICOL20): a biopolymer mimicking heparan sulfates reducing proteolytic, oxidative and nitrosative damage.
abstract: The efficacy of a chemically modified dextran - heparan sulfate mimicking regenerating agent (RGTA) on the healing of the rabbit cornea injured with alkali was examined. The eyes were injured with 0.15 N NaOH applied on the cornea or with 1.0 N NaOH using a 8 mm diameter filter paper disk. Then RGTA or placebo was applied on the cornea. In the last group of rabbits, corneas injured with the high alkali concentration were left without any treatment for four weeks; subsequently, the corneas were treated with RGTA or placebo. The central corneal thickness was measured using a pachymeter. The corneas were examined morphologically, immunohistochemically and for real time-PCR. Compared to control (unaffected) corneas, following the application of low alkali concentration the expression of urokinase-type plasminogen activator, metalloproteinase 9, nitric oxide synthase and xanthine oxidase was increased in the injured corneal epithelium of placebo-treated eyes, whereas the expression of antioxidant enzymes was reduced. Nitrotyrosine and malondialdehyde stainings appeared in the corneal epithelium. RGTA application suppressed the antioxidant/prooxidant imbalance and reduced the expression of the above-mentioned immunohistochemical markers. The corneal thickness increased after alkali injury, decreased during corneal healing after RGTA treatment faster than after placebo application. Following the injury with the high alkali concentration, corneal inflammation and neovascularization were highly pronounced in placebo-treated corneas, whereas in RGTA-treated corneas they were significantly supressed. When RGTA or placebo application was started later after alkali injury and corneas were ulcerated, subsequent RGTA treatment healed the majority of them. In conclusion, RGTA facilitates the healing of injured corneas via a reduction of proteolytic, oxidative and nitrosative damage.
authors.affiliation: Institute of Experimental Medicine, Center of Excellence, Academy of Sciences of the Czech Republic, Prague, Czech Republic. cejkova@biomed.cas.cz.
authors.forename: Jitka
authors.initials: J
authors.lastname: Cejkova
authors.affiliation: Laboratoires Thea, Clermont-Ferrand, France.
authors.forename: Celine
authors.initials: C
authors.lastname: Olmiere
authors.affiliation: Institute of Experimental Medicine, Center of Excellence, Academy of Sciences of the Czech Republic, and Czech Technical University in Prague, Faculty of Biomedical Engineering, Kladno, Czech Republic.
authors.forename: Cestmir
authors.initials: C
authors.lastname: Cejka
authors.affiliation: Institute of Experimental Medicine, Center of Excellence, Academy of Sciences of the Czech Republic, and Faculty of Natural Science, Charles University, Prague, Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Trosan
authors.affiliation: Institute of Experimental Medicine, Center of Excellence, Academy of Sciences of the Czech Republic, and Faculty of Natural Science, Charles University, Prague, Czech Republic.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Holan
mesh_terms: D000468:Alkalies / Q000633:toxicity; D000818:Animals; D001704:Biopolymers; D065306:Corneal Injuries / Q000139:chemically induced / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D006025:Glycosaminoglycans / Q000494:pharmacology*; D007150:Immunohistochemistry; D018716:Molecular Mimicry; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D059748:Proteolysis / Q000187:drug effects; D011817:Rabbits; D060888:Real-Time Polymerase Chain Reaction; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000468:Alkalies; D001704:Biopolymers; D006025:Glycosaminoglycans; C533322:OTR4120